Analisi molecolare in pazienti italiani con sindrome di Lowe

The oculocerebrorenal syndrome of Lowe (OCRL, also called OCRL1) is a rare X-linked disorder characterized by major abnormalities of eyes, nervous system, and kidneys. The gene responsible for OCRL encodes an inositol polyphosphate-5-phosphatase. We performed the molecular analysis in 20 Italian patients and we detected the mutations in all the examined patients. Sixteen mutations out of twenty consisted of truncating mutations (frameshift, nonsense, splice site and genomic deletion), and four were missense mutations. The mutations were distributed in the second half of the gene as previously described in other populations. Our results on the Italian population are similar to the data previously obtained in other populations. Herein, we also report a family with extremely skewed X inactivation that produced the full phenotype of Lowe syndrome in a female. The X chromosome inactivation studies detected an extremely skewed inactivation pattern with a ratio of 100:0 in the propositus as well as in five out of seven unaffected female relatives in four generations. The OCRL1 "de novo" mutation resides in the active paternally inherited X chromosome. X chromosome haplotype analysis suggests the presence of a locus for the familial skewed X inactivation in chromosome Xq25 most likely controlling X chromosome choice in X inactivation or cell proliferation.